Everolimus in Heart Transplantation: An Update

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, allde novoheart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

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Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Drug Design Development and Therapy ◽

10.2147/dddt.s135503 ◽

2017 ◽

Vol Volume 11 ◽

pp. 1673-1680 ◽

Cited By ~ 4

Author(s):

Matthias Helmschrott ◽

Rasmus Rivinius ◽

Thomas Bruckner ◽

Hugo A. Katus ◽

Andreas Doesch

Keyword(s):

Renal Function ◽

Heart Transplant ◽

Calcineurin Inhibitor ◽

Mammalian Target Of Rapamycin ◽

Inhibitor Therapy ◽

Target Of Rapamycin ◽

Transplant Patients

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Three Year Follow Up of the Randomized SCHEDULE Trial With Everolimus Initiation and Early Withdrawal of Calcineurin Inhibitor Therapy in De Novo Heart Transplant Recipients - A Multicenter, Randomized Scandinavian Trial

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2015.01.346 ◽

2015 ◽

Vol 34 (4) ◽

pp. S129-S130

Author(s):

A.K. Andreassen ◽

B. Andersson ◽

F. Gustafsson ◽

H. Eiskjær ◽

G. Rådegran ◽

...

Keyword(s):

Heart Transplant ◽

Calcineurin Inhibitor ◽

De Novo ◽

Inhibitor Therapy ◽

Transplant Recipients ◽

Early Withdrawal ◽

Heart Transplant Recipients

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Clinical Experience With Certican® (Everolimus) in De Novo Heart Transplant Patients at the Deutsches Herzzentrum Berlin

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2005.01.011 ◽

2005 ◽

Vol 24 (4) ◽

pp. S201-S205 ◽

Cited By ~ 25

Author(s):

Hans Lehmkuhl ◽

Roland Hetzer

Keyword(s):

Clinical Experience ◽

Heart Transplant ◽

De Novo ◽

Transplant Patients

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Everolimus Initiation With Calcineurin Inhibitor Withdrawal Reduces Allograft Vasculopathy in De-Novo Heart Transplant Recipients

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2014.01.412 ◽

2014 ◽

Vol 33 (4) ◽

pp. S154 ◽

Cited By ~ 2

Author(s):

S. Arora ◽

B. Andersson ◽

F. Gustafsson ◽

H. Eiskjær ◽

G. Rådegran ◽

...

Keyword(s):

Heart Transplant ◽

Calcineurin Inhibitor ◽

De Novo ◽

Transplant Recipients ◽

Allograft Vasculopathy ◽

Heart Transplant Recipients

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Usefulness of Speckle Tracking Echocardiography and Biomarkers for Detecting Acute Cellular Rejection After Heart Transplantation

10.21203/rs.3.rs-96047/v1 ◽

2020 ◽

Author(s):

Cecília Beatriz Bittencourt Viana Cruz ◽

Ludhmila A. Hajjar ◽

Fernando Bacal ◽

Marco S. Lofrano-Alves ◽

Márcio S.M. Lima ◽

...

Keyword(s):

Heart Transplantation ◽

Right Ventricular ◽

Speckle Tracking ◽

Troponin I ◽

Speckle Tracking Echocardiography ◽

Left Ventricular ◽

Acute Cellular Rejection ◽

Control Group ◽

Transplant Patients ◽

Cellular Rejection

Abstract Background: Acute cellular rejection (ACR) is a major complication after heart transplantation. Endomyocardial biopsy (EMB) remains the gold standard for its diagnosis, but it has concerning complications. We evaluated the usefulness of speckle tracking echocardiography (STE) and biomarkers for detecting ACR after heart transplantation.Methods: We prospectively studied 60 transplant patients with normal left and right ventricular systolic function who underwent EMB for surveillance six months after transplantation. Sixty age- and sex-matched healthy individuals constituted the control group. Conventional echocardiographic parameters, left ventricular global longitudinal, radial and circumferential strain (LV-GLS, LV-GRS and LV-GCS, respectively), left ventricular systolic twist (LV-twist) and right ventricular free wall longitudinal strain (RV-FWLS) were analyzed just before the procedure. We also measured biomarkers at the same moment. Results: Among the included 60 patients, 17 (28%) had severe ACR (grade ≥ 2R), and 43 (72%) had no significant ACR (grade 0 – 1R). The absolute values of LV-GLS, LV-twist and RV-FWLS were lower in transplant patients with ACR degree ≥ 2 R than in those without ACR (12.5% ± 2.9% vs 14.8% ± 2.3%, p=0.002; 13.9° ± 4.8° vs 17.1° ± 3.2°, p=0.048; 21.4%± 3.2% vs 16.6% ± 2.9%, p<0.001; respectively), while no differences were observed between the LV-GRS or LV-GCS. All of these parameters were lower in the transplant group without ACR than in the nontransplant control group, except for the LV-twist. Cardiac troponin I levels were significantly higher in patients with significant ACR than in patients without significant ACR [0.19 ng/mL (0.09–1.31) vs. 0.05 ng/mL (0.01–0.18), p=0.007]. The combination of troponin with LV-GLS, RV FWLS and LV-Twist had an AUC (area under curve) for the detection of ACR of 0.80 (0.68 – 0.92), 0.89 (0.81 – 0.93) and 0.79 (0.66 – 0.92), respectively. Conclusion: Heart transplant patients have altered left ventricular dynamics compared with control individuals. The combination of troponin with strain parameters had higher accuracy for the detection of ACR than the isolated variables and this association might select patients with a higher risk for ACR who will benefit from an EMB procedure in the first year after heart transplantation.

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Abstract 13933: High Urgency Candidates for Heart Transplantation Does Not Correlate to the Development of Primary Graft Dysfunction

Circulation ◽

10.1161/circ.142.suppl_3.13933 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Rafael Skorka ◽

Keith Nishihara ◽

Adriana Shen ◽

Evan P Kransdorf ◽

Lillian Benck ◽

...

Keyword(s):

Heart Transplantation ◽

Heart Transplant ◽

Survival Rates ◽

Control Group ◽

High Dose ◽

Primary Graft Dysfunction ◽

Graft Dysfunction ◽

Assist Device ◽

Transplant Patients ◽

High Urgency

Introduction: Primary Graft Dysfunction (PGD) after Heart Transplantation (HTx) is seen in approximately 7-30% of heart transplant patients as described by the literature. Many of these patients have severe PGD which requires support with ECMO. It has been reported that patients who are severely ill on high dose inotropes or on assists devices have greater propensity to develop severe PGD. Many of these patients have borderline blood pressure due to poor cardiac function which may contribute to PGD with its associated vasoplegia. In order to asses risk for the development of PGD we evaluated our patients in terms of their status at the time of transplant to assess risk. Methods: Between 2010 and 2019 we assessed 44 Heart Transplant patients who developed severe PGD immediately after HTx. The UNOS Status at the time of Transplant was recorded along with the presence of a durable assist device, temporary assist device, or no Inotropes or assist device. 30 Day and 1 Year survival were assessed for all status groups including a control group (no PGD, n=799). Results: High urgency status at the time of transplant was not the overwhelming majority of patients that developed severe PGD. Approximately 32% of these patients were patients who were waiting for transplant at home, who were not on Intravenous Inotropes and not on assist devices. 1 Year survival was compromised in all patients who developed severe PGD with survival rates that were significantly lower than patients without PGD in our program (47.7% vs 93.6%, p<0.001) (see Table). Conclusions: High urgency status is not solely associated with the development of severe PGD. Further assessment into these non-urgent patients who develop severe PGD is warranted and is under investigation. Inflammatory markers should be assessed in all patients who develop severe PGD.

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Enhanced brain natriuretic peptide response to peak exercise in heart transplant recipients

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.6.2270 ◽

1998 ◽

Vol 85 (6) ◽

pp. 2270-2276 ◽

Cited By ~ 24

Author(s):

Bernard Geny ◽

Anne Charloux ◽

Eliane Lampert ◽

Jean Lonsdorfer ◽

Pascal Haberey ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Heart Transplantation ◽

Left Ventricular Mass ◽

Heart Transplant ◽

Left Ventricular Mass Index ◽

Left Ventricular ◽

Peak Exercise ◽

Transplant Recipients ◽

Heart Transplant Recipients

We investigated the atrial (ANP) and brain natriuretic peptides (BNP), catecholamines, heart rate, and blood pressure responses to graded upright maximal cycling exercise of eight matched healthy subjects and cardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP (15.2 ± 3.7 vs. 4.4 ± 0.8 pmol/l; P < 0.01) and BNP (14.3 ± 2.6 vs. 7.4 ± 0.6 pmol/l; P< 0.01), were elevated in HTR, but catecholamine levels were similar in both groups. Peak exercise O2uptake and heart rate were lower in HTR. Exercise-induced maximal ANP increase was similar in both groups (167 ± 34 vs. 216 ± 47%). Enhanced BNP increase was significant only in HTR (37 ± 8 vs. 16 ± 8%; P < 0.05). Similar norepinephrine but lower peak epinephrine levels were observed in HTR. ANP and heart rate changes from rest to 75% peak exercise were negatively correlated ( r = −0.76, P < 0.05), and BNP increase was correlated with left ventricular mass index ( r = 0.83, P < 0.01) after heart transplantation. Although ANP increase was not exaggerated, these data support the idea that the chronotropic limitation secondary to sinus node denervation might stimulate ANP release during early exercise in HTR. Furthermore, the BNP response to maximal exercise, which is related to the left ventricular mass index of HTR, is enhanced after heart transplantation.

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Antibody-mediated rejection with detection of de novo donor-specific anti-human leucocyte antigen Class II antibodies 3 years after heart transplantation: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytz246 ◽

2020 ◽

Vol 4 (1) ◽

pp. 1-4

Author(s):

Bernd Ludwig ◽

Johanna Schneider ◽

Daniela Föll ◽

Qian Zhou

Keyword(s):

Heart Transplantation ◽

De Novo ◽

Survival Rates ◽

Graft Function ◽

Left Ventricular ◽

Cardiac Allograft ◽

Left Ventricular Ejection ◽

High Dose ◽

Ventricular Ejection Fraction ◽

Antibody Mediated Rejection

Abstract Background Antibody-mediated rejection (AMR) in cardiac transplantation may manifest early within the first weeks after transplantation but also late after months to years following transplantation resulting in mild heart failure to cardiogenic shock. While patients with early cardiac AMR are less affected and seem to have survival rates comparable to transplant recipients without AMR, late cardiac AMR is frequently associated with graft dysfunction, fulminant forms of cardiac allograft vasculopathy, and a high mortality rate. Nevertheless, AMR of cardiac allografts remains difficult to diagnose and to treat. Case summary We report the case of a 47-year-old male patient with late AMR of the cardiac allograft 3 years after heart transplantation. Antibody-mediated rejection was confirmed by endomyocardial biopsy and the presence of donor-specific antibodies (DSA). The patient was treated with high dose of prednisolone, plasmapheresis, intravenous Gamma Globulin, rituximab, immunoadsorption, and bortezomib. Under this treatment regimen left ventricular ejection fraction and pro B-type natriuretic peptide recovered, and the patient improved to New York Heart Association Class I. Currently, 3 years after the diagnosis of cardiac AMR, graft function continues to be nearly normal, and there is no evidence for transplant vasculopathy. Discussion This case illustrates that AMR can occur at any time after transplantation. Although graft function fully recovered after treatment in our patient, the level of DSA remained high, suggesting that DSA may not be a reliable parameter to determine the intensity and duration of the therapy.

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